Progress in human molecular and medical genetics depends on the efficient and accurate detection of mutations and sequence polymorphisms. There is an increasing list of genes with medically significant alleles, i.e. alleles responsible for disease or susceptibility to disease, for which there are many alleles with the disease-associated phenotype (e.g. p53, BRCA1, BRCA2, hMSH2, hMLH). IMBP (Immobilized Mismatch Binding Protein) may be the ideal partner to pair with sequencing for high through-put diagnostics of disease related genes with multiple alleles. IMBP assays could be used to rapidly and inexpensively screen samples for the presence of any mutation in a large number of specific DNA fragments. Any samples test positive, i.e., containing sequence differences from wild type or some reference sequence, would be sequenced to determine the precise mutation. No further processing would be required for those samples testing negative, i.e, containing only sequences identical to the reference sequence. It is the aim of this project to develop a prototype "mutation scanning" kit using the tumor suppressor gene p53 as a model system and to expand the scope of the mutations detected to include larger additions and deletions. PROPOSED COMMERCIAL APPLICATION: An assay to allow rapid an inexpensive scanning of entire genes has immediate commercial applications in both human diagnostics and research markets. Genes such as p53, BRCA1 AND BRCA2, which are already being examined in clinical diagnostics would be ideal subjects for the scanning system described herein. It is reasonable to expect that additional genes with similar mutation patterns will continue to be discovered, particularly involved with oncology. A mutation scanning technology would be useful both in the search for relevant mutations and in the development of clinical diagnostics.